Maria remains a significant health threat to humans despite massive international attempts to eradicate the disease. Over 200 million people are said to have malaria and over one million deaths per year are associated with malaria in Africa alone.
Malaria is a disease of warm blooded animals caused by infection with a parasite of the genus Plasmodium. Four species, P. vivax, P. falciparum, P. malariae, and P. ovale, are known to infect humans. The parasite is transmitted to humans by the bite of Anopheles mosquitoes. Subsequent to mosquito bite, the parasite rapidly invades the blood cells of the victim. After an incubation period, generally lasting about 10 to 14 days, symptoms, consisting of chills, fever, headache, muscle pains, splenomegaly, and anemia, appear. This incubation period may be prolonged for many weeks and onset can be quite insidious. Red blood cells are at first altered and later destroyed by the infection. After an acute episode, the victim may be reinfected by the parasite which persists in the liver.
Drug therapy utilizing quinine, chloroquine, primaquine, and other agents has been the mainstay of therapy against malaria. However, drug-resistant strains of protozoa have developed and in some cases strains are resistant to many or all of the current therapeutic agents. In particular, P. falciparum malaria is quite prone to exhibit single and even multiple drug-resistance. While new agents are continually developed and introduced, resistance to such new agents also quickly develops. For example, mefloquine-resistant malaria was reported even before mefloquine licensure was completed. There is, thus, an urgent need for antimalarial agents which can be used in the treatment of drug-resistant malaria.